The use of recombinant host cells in the expression of heterologous proteins has in recent years greatly simplified the production of large quantities of commercially valuable proteins, which otherwise are obtainable only by purification from their native sources. Currently, there is a varied selection of expression systems from which to choose for the production of any given protein, including prokaryotic and eukaryotic hosts. The selection of an appropriate expression system will often depend not only on the ability of the host cell to produce adequate yields of the protein in an active state, but also to a large extent may be governed by the intended end use of the protein.
Although mammalian and yeast cells have been the most commonly used eukaryotic hosts, filamentous fungi have now begun to be recognized as very useful as host cells for recombinant protein production. Certain species of the genus Aspergillus have been used effectively as host cells for recombinant protein production. Furthermore, there are often problems with the formation of too dense aggregates of mycelium and uneven distribution, which also results in starvation for nutrients and an unproductive situation. The species Aspergillus nidulans has been reported to be transformed with recombinant plasmids (Ballance, et al. Biochem. Biophys. Res. Comm. 112:284-289, 1983), but transformation was found to occur at fairly low frequency. Both Aspergillus niger and Aspergillus oryzae have also been described as being useful in recombinant production of heterologous proteins. Although these species are currently routinely used in recombinant protein production, they are not without their drawbacks. In particular, their growth morphology in fermentors are not optimum for fermentation, as viscosity tends to become rather high as biomass increases. Increased viscosity limits the ability to mix and aerate the fermentation culture, leading to oxygen and nutrient starvation of the mycelia, which therefore become inviable and unproductive. Furthermore, there are often problems with the formation of too dense aggregates of mycelium, and uneven distribution, which also results in starvation for nutrients. Therefore, for commercial purposes, there continues to be a need for fungal hosts which are capable of use in expression of recombinant proteins but which exhibit satisfactory growth characteristics, such as rapid growth and low viscosity, thereby enhancing productivity in fermentors.